Cervical cancer continues to be the 1st or 2nd leading cause of cancer death among women in low- and middle- income countries. In the U.S., low socioeconomic status (SES) is strongly correlated with poor cervical cancer survival. In resource-limited settings in the U.S. and abroad, there is a significant need for new point-of-care diagnostics that enable combined detection and treatment of cervical precancer in a single visit. To date, global attempts to implement see & treat protocols have been limited by the extremely low specificity of the three existing diagnostic approaches that can be used at the point-of-care. See & treat protocols based on imaging (colposcopy or visual inspection with acetic acid (VIA)) or biomarker detection (HPV DNA testing) result in high rates of overtreatment, subjecting patients to unnecessary procedures and wasting healthcare resources. We hypothesize that a combination of imaging and biomarker detection can reduce the high false positive rate of current cervical screening tools. Increased nuclear-to-cytoplasmic (N/C) ratio is one of the best known phenotypic biomarkers of cervical precancer, but can currently only be assessed from cytology or biopsy. We have developed an investigational imaging method, high-resolution microendoscopy (HRME), to identify cervical lesions in situ with increased N/C ratio. In Aim 1, we will adapt the HRME to a mobile platform which incorporates a cell phone to capture, display, analyze, and transmit images. We will then evaluate the performance of the mobile HRME (mHRME) with an existing biomarker (HPV DNA testing) and an investigational biomarker (HPV E7 oncoprotein). In Aim 2, we will evaluate performance of the mHRME in two globally relevant contexts: (A) in a clinical evaluation of 429 women in the U.S., we will assess whether addition of mHRME imaging improves specificity of colposcopy, without significantly reducing sensitivity; (B) in a clinical evaluation of 4,592 women in El Salvador, we will assess whether mHRME imaging improves the specificity of screening by VIA alone, HPV DNA testing alone, or with HPV DNA testing followed by VIA. Overexpression of HPV E7 oncoprotein is one of the best known molecular biomarkers of cervical precancer. To further improve specificity of molecular testing, in Aim 3 we will develop a rapid, low-cost, laterl flow test to detect E7. We will assess test performance using cervical specimens in a nested case-control of 270 patients with and without cervical precancer who participated in Aim 2. This work will provide clinicians in the U.S. and globally with robust, affordable, integrated, point-of care tools to directly image phenotypic changes and detect molecular markers associated with the development and progression of cervical precancer, addressing the poor specificity of current methods. Together, these tools will improve the efficacy and cost-effectiveness of early detection of cervical precancer, allowing diagnosis and treatment in a single visit to prevent the development of invasive cervical cancer.